Dose-, IGF-I- and sex-dependent changes in lipid profile and body composition during GH replacement therapy in adult onset GH deficiency

OBJECTIVE: Patients with GH deficiency of adult onset (GHDA) exhibit dyslipidaemia and increased cardiovascular morbidity. GH replacement potently reduces body fat and serum lipids in GHDA. In recent years, lower GH doses have been introduced. The purpose of this analysis was to explore the response relationship between GH doses, lipids and body composition. DESIGN: Two consecutive, randomized 12-month GH replacement studies covering placebo and three different doses of GH (0.5, 1.0 and 1.7 IU/m(2) per day). Low and intermediate doses were IGF-I titrated. PATIENTS: Fifty-eight patients with severe GHDA, not previously treated with GH and stably substituted for other endocrine deficiencies, were included in the study. METHODS: Serum lipoproteins, serum IGF-I and body composition analysis by dual energy X-ray absorptiometry (DXA) were used. RESULTS: Fifty-seven percent of patients exhibited low density lipoprotein (LDL) cholesterol levels above 4.16 mmol/l, corresponding to the American Heart Association threshold of 160 mg/dl. GH treatment resulted in significant decreases in total and LDL cholesterol, with no significant change in high density lipoprotein cholesterol or triglycerides. The low dose induced no significant changes in lipid levels, whereas the medium dose reduced LDL cholesterol and the high dose decreased both LDL and total cholesterol. The effects depended significantly on the GH dose and the level of IGF-I obtained, but not on gender. GH replacement induced dose-dependent reductions in fat mass and sex-dependent increases in lean mass. CONCLUSIONS: GH given for 1 year at a dosage between 0.5 and 1.7 IU/m(2) per day reduced fat mass in a dose-dependent manner, increased lean body mass and lowered total and LDL cholesterol in patients with severe GHDA. Low dose GH treatment with normal IGF-I levels induced smaller changes compared with high dose therapy, and may need a longer treatment time.     

Protective effect of melatonin on liver ischemia-reperfusion induced pulmonary microvascular injury in rats

Objective

Reactive oxygen species generated during liver reperfusion have been implicated in remote lung injury. In this study, we evaluate the protective effects of melatonin pretreatment against the increased pulmonary microvascular permeability.

Methods

Male Sprague-Dawley rats were divided into three groups: shame-operated, liver ischemia-reperfusion (I/R), and melatonin pretreated (15 mg/kg, intraperitoneally) 15 minutes prior to the liver I/R). The duration of ischemia was 30 minutes, followed by 2 hours of reperfusion. Lungs were isolated in situ and parameters of the capillary filtration coefficient (K_fc), lung wet-to-dry weight ratio (W/D), lung weight-to-body weight (LW/BW), and protein concentration in bronchial lavage fluid (PCBAL), the percentage of macrophages and neutrophils in bronchial lavage fluid (BALF), and lung tissue malonedealdehyde were used to assess the lung injury.

Results

Liver I/R-induced lung injury was noted by the markedly increased K_fc, W/D, LW/BW, PCBAL, and the presence of neutrophils and macrophages in BALF. Lipid peroxidation was also increased (P < .05). All indicators were markedly decreased in melatonin-pretreated rats (P < .05), suggesting that lung injury was attenuated.

Conclusions

Melatonin pretreatment prior to liver I/R can effectively reduce the pulmonary microvascular permeability and attenuate lipid peroxidation in the lungs.     

Functional characterisation of a complex mutation in the α(1,4)galactosyltransferase gene in Taiwanese individuals with p phenotype

Background and objective: Individuals with p phenotype lack P1, P^k and P antigens on red blood cells, presumably as a result of deficiency in the enzyme α(1,4)galactosyltransferase (A4GALT). The aim of this study was to explore the molecular background of a Taiwanese family with p phenotype. Materials and methods: Blood samples from two p siblings and seven family members were investigated. The coding region of the A4GALT gene was analysed by polymerase chain reaction and direct sequencing. The wild‐ and mutant‐complementary DNAs (cDNAs) of A4GALT were cloned into an expression vector and transfected to Chinese hamster ovary (CHO) cells. P^k expression on the transfected cells was analysed by flow cytometry and the activities of A4GALT were measured by high‐performance liquid chromatography. Results: The two individuals with p phenotype were homozygous for the complex mutation, which was caused by a combined deletion and insertion between nt 418 and 428. No expression of P^k and no enzyme activity were observed in cells transfected with the mutant construct. Conclusion: The first case of p phenotype in Taiwan was caused by a non‐functional allele resulting from a homozygous complex mutation of A4GALT gene.     

Designing for reduced operating costs in a maternity unit

Operating costs of hospitals make great demands on resources. This paper describes the possibility of using the methodology of linear systems to find ways for designing for reduced operating costs in a maternity unit in England. The organizational framework of the United Kingdom National Health Service, and its capital planning processes are outlined. Capital cost control methods used in building English hospitals are explained and then the early stages of an experiment in which the step response of an injection of capital to a capital building project are described. The project itself is in a maternity unit. Maternity has been chosen because it is particularly suitable for this kind of experiment having a relatively well defined input and output, and well established indicators of clinical outcome. It is hoped that insight into the step response will shed light on new ways of designing for reduced operating costs.     

Pr?operative Aufkl?rung über neue Operationsstrategien: Interaktive Software zur Verbesserung der Patienteninformation

Hintergrund   

Im Kontext innovativer klinischer Forschung müssen Patienten in angemessener Form über neuartige chirurgische Strategien informiert werden. Bereits unter Alltagsbedingungen wurde die Qualität der chirurgischen Aufklärung in empirischen Studien als wesentliche Schwachstelle identifiziert. Die Bedeutung der präoperativen Aufklärung in zivilrechtlichen Verfahren zwingt zur Elimination dieser Schwachstelle gerade dann, wenn durch Anwendung neuer chirurgischer Konzepte die Unsicherheit und Unüberschaubarkeit der perioperativen Situation für den Patienten zunimmt.